11-5698520-G-C

Variant names:

• chr11-5698520-G-C
• rs1063303
• NM_006074.5:c.725G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006074.5(TRIM22):​c.725G>C​(p.Arg242Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,612,768 control chromosomes in the GnomAD database, including 244,870 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19685 hom., cov: 32)
  • Exomes 𝑓: 0.55 (225185 hom.)
• Consequence: TRIM22 NM_006074.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0650
• Publications: 39 publications found

Genes affected

TRIM22 (HGNC:16379): (tripartite motif containing 22) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon. The protein is involved in innate immunity against different DNA and RNA viruses. [provided by RefSeq, Oct 2021]

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.948533E-6).
• BP6: Variant 11-5698520-G-C is Benign according to our data. Variant chr11-5698520-G-C is described in ClinVar as Benign. ClinVar VariationId is 2688046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006074.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM22	NM_006074.5	MANE Select	c.725G>C	p.Arg242Thr	missense	Exon 4 of 8	NP_006065.2
	TRIM22	NM_001199573.2		c.713G>C	p.Arg238Thr	missense	Exon 4 of 8	NP_001186502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM22	ENST00000379965.8	TSL:1 MANE Select	c.725G>C	p.Arg242Thr	missense	Exon 4 of 8	ENSP00000369299.3
	TRIM5	ENST00000412903.1	TSL:1	c.-61-18282C>G		intron	N/A	ENSP00000388031.1
	TRIM22	ENST00000454828.6	TSL:5	c.629G>C	p.Arg210Thr	missense	Exon 3 of 7	ENSP00000393250.2

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75591 AN: 151940 Hom.: 19677 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.485

GnomAD2 exomes AF: 0.500 AC: 124121 AN: 248092 AF XY: 0.511

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.187

Gnomad FIN exome AF: 0.618

Gnomad NFE exome AF: 0.570

Gnomad OTH exome AF: 0.525

GnomAD4 exome AF: 0.548 AC: 800183 AN: 1460710 Hom.: 225185 Cov.: 48 AF XY: 0.549 AC XY: 398720 AN XY: 726574

African (AFR) AF: 0.387 AC: 12945 AN: 33456

American (AMR) AF: 0.370 AC: 16505 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 14093 AN: 26118

East Asian (EAS) AF: 0.141 AC: 5610 AN: 39668

South Asian (SAS) AF: 0.543 AC: 46809 AN: 86196

European-Finnish (FIN) AF: 0.613 AC: 32710 AN: 53386

Middle Eastern (MID) AF: 0.476 AC: 2711 AN: 5700

European-Non Finnish (NFE) AF: 0.573 AC: 636759 AN: 1111262

Other (OTH) AF: 0.531 AC: 32041 AN: 60338

GnomAD4 genome AF: 0.497 AC: 75624 AN: 152058 Hom.: 19685 Cov.: 32 AF XY: 0.498 AC XY: 37011 AN XY: 74316

African (AFR) AF: 0.391 AC: 16206 AN: 41446

American (AMR) AF: 0.454 AC: 6948 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1897 AN: 3472

East Asian (EAS) AF: 0.182 AC: 942 AN: 5176

South Asian (SAS) AF: 0.546 AC: 2631 AN: 4820

European-Finnish (FIN) AF: 0.619 AC: 6537 AN: 10562

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38789 AN: 67984

Other (OTH) AF: 0.487 AC: 1025 AN: 2106

Alfa AF: 0.473 Hom.: 2625

Bravo AF: 0.469

TwinsUK AF: 0.582 AC: 2157

ALSPAC AF: 0.579 AC: 2231

ESP6500AA AF: 0.395 AC: 1598

ESP6500EA AF: 0.570 AC: 4787

ExAC AF: 0.504 AC: 60970

Asia WGS AF: 0.428 AC: 1490 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.060	T
MetaRNN	Benign	0.0000080	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.065
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.038
Sift	Benign	0.036	D
Sift4G	Uncertain	0.021	D
Polyphen		0.0010	B
Vest4		0.076
MPC		0.073
ClinPred		0.011	T
GERP RS		-2.1
Varity_R		0.10
gMVP		0.060
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1063303; hg19: chr11-5719750; COSMIC: COSV66090500; COSMIC: COSV66090500;